Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway.
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Date
2012-12
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Abstract
Swainsonine, a natural indolizidine alkaloid, has been reported to have antitumour effects, and can induce apoptosis in
human gastric and lung cancer cells. In the present study, we evaluated the antitumour effects of swainsonine on several
oesophageal squamous cell carcinoma cells and investigated relative molecular mechanisms. Swainsonine treatment
inhibited the growth of Eca-109, TE-1 and TE-10 cells in a concentration-dependent manner as measured by MTT assay.
Morphological observation, DNA laddering detection and flow cytometry analysis demonstrated that swainsonine treatment
induced Eca-109 cell apoptosis in vitro. Further results showed that swainsonine treatment up-regulated Bax, downregulated
Bcl-2 expression, triggered Bax translocation to mitochondria, destructed mitochondria integrity and
activated mitochondria-mediated apoptotic pathway, followed by the release of cytochrome c, which in turn activated
caspase-9 and caspase-3, promoted the cleavage of PARP, resulting in Eca-109 cell apoptosis. Moreover, swainsonine
treatment inhibited Bcl-2 expression, promoted Bax translocation, cytochrome c release and caspase-3 activation in
xenograft tumour cells, resulting in a significant decrease of tumour volume and tumour weight in the swainsoninetreated
xenograft mice groups compared with that in the control group. Taken together, this study demonstrated that
swainsonine inhibited Eca-109 cells growth through activation of mitochondria-mediated caspase-dependent pathway.
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Keywords
Apoptosis, caspase, Eca-109 cells, mitochondrial pathway, swainsonine
Citation
Li Zhaocai, Huang Yong, Dong Feng, Li Wei, Ding Li, Yu Gaoshui, Xu Dan, Yang Yuanyuan, Xu Xingang, Tong Dewen. Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway. Journal of Biosciences. 2012 Dec; 37 (6): 1005-1016.